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  • 1
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    Disc reflection and a possible disc wind during a soft X-ray state in the neutron star low-mass X-ray binary 1RXS J180408.9-342058 (2016)
    Oxford University Press
    Details
    Publication Date: 2016-07-29
    Description: 1RXS J180408.9–342058 is a transient neutron star low-mass X-ray binary that exhibited a bright accretion outburst in 2015. We present NuSTAR , Swift , and Chandra observations obtained around the peak brightness of this outburst. The source was in a soft X-ray spectral state and displayed an X-ray luminosity of L X ~= (2–3)  x  10 37 ( D /5.8 kpc) 2 erg s –1 (0.5–10 keV). The NuSTAR data reveal a broad Fe–K emission line that we model as relativistically broadened reflection to constrain the accretion geometry. We found that the accretion disc is viewed at an inclination of i ~= 27°–35° and extended close to the neutron star, down to R in ~= 5–7.5 gravitational radii (~=11–17 km). This inner disc radius suggests that the neutron star magnetic field strength is B 2  x  10 8  G. We find a narrow absorption line in the Chandra /HEG data at an energy of ~=7.64 keV with a significance of ~=4.8. This feature could correspond to blueshifted Fe  xxvi and arise from an accretion disc wind, which would imply an outflow velocity of v out ~= 0.086 c (~=25 800 km s –1 ). However, this would be extreme for an X-ray binary and it is unclear if a disc wind should be visible at the low inclination angle that we infer from our reflection analysis. Finally, we discuss how the X-ray and optical properties of 1RXS J180408.9–342058 are consistent with a relatively small ( P orb 3 h) binary orbit.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 2
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    Moderate drop in water table increases peatland vulnerability to post-fire regime shift (2015)
    Springer Nature
    Details
    Publication Date: 2015-01-28
    Description: Northern and tropical peatlands represent a globally significant carbon reserve accumulated over thousands of years of waterlogged conditions. It is unclear whether moderate drying predicted for northern peatlands will stimulate burning and carbon losses as has occurred in their smaller tropical counterparts where the carbon legacy has been destabilized due to severe drainage and deep peat fires. Capitalizing on a unique long-term experiment, we quantify the post-wildfire recovery of a northern peatland subjected to decadal drainage. We show that the moderate drop in water table position predicted for most northern regions triggers a shift in vegetation composition previously observed within only severely disturbed tropical peatlands. The combined impact of moderate drainage followed by wildfire converted the low productivity, moss-dominated peatland to a non-carbon accumulating shrub-grass ecosystem. This new ecosystem is likely to experience a low intensity, high frequency wildfire regime, which will further deplete the legacy of stored peat carbon. Scientific Reports 5 doi: 10.1038/srep08063
    Electronic ISSN: 2045-2322
    Topics: Natural Sciences in General
    Published by Springer Nature
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  • 3
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    From dynamic combinatorial 'hit' to lead: in vitro and in vivo activity of compounds targeting the pathogenic RNAs that cause myotonic dystrophy (2012)
    Oxford University Press
    Details
    Publication Date: 2012-07-22
    Description: The myotonic dystrophies (DM) are human diseases in which the accumulation of toxic RNA (CUG or CCUG) repeats in the cell causes sequestration of splicing factors, including MBNL1, leading to clinical symptoms such as muscle wasting and myotonia. We previously used Dynamic Combinatorial Chemistry to identify the first compounds known to inhibit (CUG)-MBNL1 binding in vitro . We now report transformation of those compounds into structures with activity in vivo . Introduction of a benzo[g]quinoline substructure previously unknown in the context of RNA recognition, as well as other modifications, provided several molecules with enhanced binding properties, including compounds with strong selectivity for CUG repeats over CAG repeats or CAG–CUG duplex RNA. Compounds readily penetrate cells, and improve luciferase activity in a mouse myoblast assay in which enzyme function is coupled to a release of nuclear CUG–RNA retention. Most importantly, two compounds are able to partially restore splicing in a mouse model of DM1.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 4
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    Evidence for erythrocyte-binding antigen 175 as a component of a ligand-blocking blood-stage malaria vaccine [Microbiology] (2011)
    National Academy of Sciences
    Details
    Publication Date: 2011-05-04
    Description: The ligands that pathogens use to invade their target cells have often proven to be good targets for vaccine development. However, Plasmodium falciparum has redundant ligands that mediate invasion of erythrocytes. The first requirement for the development of a successful ligand-blocking malaria vaccine is the demonstration that antibodies induced to each ligand can block the erythrocyte invasion of parasites with polymorphic sequences. Because of P. falciparum’s redundancy in erythrocyte invasion, each ligand needs to be studied under artificial conditions in which parasite invasion is restricted in its use of alternative pathways. Here we investigate the role of erythrocyte-binding antigen 175 (EBA-175), a parasite ligand that binds to sialic acid on glycophorin A, in the invasion of erythrocytes by 10 P. falciparum clones under conditions in which invasion is partially limited to the EBA-175–glycophorin A pathway, using chymotrypsin-treated erythrocytes. We show that the ability to invade erythrocytes for both sialic acid–independent and sialic acid–dependent pathways requires the EBA-175–glycophorin A pathway for erythrocyte invasion. Importantly, antibodies against region II of EBA-175 from the 3D7 clone blocked invasion of chymotrypsin-treated erythrocytes by 〉50% by all parasite clones studied, including those with multiple different mutations described in the literature. The one exception was FCR3, which had a similar sequence to 3D7 but only 30% inhibition of invasion of chymotrypsin-treated erythrocytes, indicating alternative pathways for invasion of chymotrypsin-treated erythrocytes. Our findings suggest that antibodies to region II of EBA-175, as one component of a ligand-blocking malaria vaccine, are largely unaffected by polymorphism in EBA-175.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 5
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    Ferroportin is important for heart function [Systems Biology] (2015)
    National Academy of Sciences
    Details
    Publication Date: 2015-03-11
    Description: Iron is essential to the cell. Both iron deficiency and overload impinge negatively on cardiac health. Thus, effective iron homeostasis is important for cardiac function. Ferroportin (FPN), the only known mammalian iron-exporting protein, plays an essential role in iron homeostasis at the systemic level. It increases systemic iron availability by...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 6
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    Broad absorption line variability in radio-loud quasars (2014)
    Oxford University Press
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    Publication Date: 2014-04-07
    Description: We investigate C iv broad absorption line (BAL) variability within a sample of 46 radio-loud quasars (RLQs), selected from Sloan Digital Sky Survey (SDSS)/Faint Images of the Radio Sky at Twenty-Centimeters (FIRST) data to include both core-dominated (39) and lobe-dominated (7) objects. The sample consists primarily of high-ionization BAL quasars, and a substantial fraction have large BAL velocities or equivalent widths; their radio luminosities and radio-loudness values span ~2.5 orders of magnitude. We have obtained 34 new Hobby-Eberly Telescope spectra of 28 BAL RLQs to compare to earlier SDSS data, and we also incorporate archival coverage (primarily dual-epoch SDSS) for a total set of 78 pairs of equivalent width measurements for 46 BAL RLQs, probing rest-frame time-scales of ~80–6000 d (median 500 d). In general, only modest changes in the depths of segments of absorption troughs are observed, akin to those seen in prior studies of BAL radio-quiet quasars (RQQs). Also similar to previous findings for RQQs, the RLQs studied here are more likely to display BAL variability on longer rest-frame time-scales. However, typical values of $|{\Delta }{\rm EW}|$ and $|{\Delta }{\rm EW}|/{\langle }{\rm EW}{\rangle }$ are ~40 ± 20 per cent lower for BAL RLQs when compared with those of a time-scale-matched sample of BAL RQQs. Optical continuum variability is of similar amplitude in BAL RLQs and BAL RQQs; for both RLQs and RQQs, continuum variability tends to be stronger on longer time-scales. BAL variability in RLQs does not obviously depend upon their radio luminosities or radio-loudness values, but we do find tentative evidence for greater fractional BAL variability within lobe-dominated RLQs. Enhanced BAL variability within more edge-on (lobe-dominated) RLQs supports some geometrical dependence to the outflow structure.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 7
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    FSH rerouting and ovarian function [Physiology] (2014)
    National Academy of Sciences
    Details
    Publication Date: 2014-04-16
    Description: FSH and luteinizing hormone (LH) are secreted constitutively or in pulses, respectively, from pituitary gonadotropes in many vertebrates, and regulate ovarian function. The molecular basis for this evolutionarily conserved gonadotropin-specific secretion pattern is not understood. Here, we show that the carboxyterminal heptapeptide in LH is a gonadotropin-sorting determinant in vivo...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 8
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    Assessment. School performance will fail to meet legislated benchmarks (2008)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2008-09-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bryant, M J -- Hammond, K A -- Bocian, K M -- Rettig, M F -- Miller, C A -- Cardullo, R A -- New York, N.Y. -- Science. 2008 Sep 26;321(5897):1781-2. doi: 10.1126/science.1161033.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, University of California, Riverside, Riverside, CA 92521, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18818344" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 9
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    A rapidly changing jet orientation in the stellar-mass black-hole system V404 Cygni (2019)
    Springer Nature
    In: Nature
    Details
    Publication Date: 2019
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Springer Nature
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  • 10
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    Whole-genome analysis informs breast cancer response to aromatase inhibition (2012)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2012-06-23
    Description: To correlate the variable clinical features of oestrogen-receptor-positive breast cancer with somatic alterations, we studied pretreatment tumour biopsies accrued from patients in two studies of neoadjuvant aromatase inhibitor therapy by massively parallel sequencing and analysis. Eighteen significantly mutated genes were identified, including five genes (RUNX1, CBFB, MYH9, MLL3 and SF3B1) previously linked to haematopoietic disorders. Mutant MAP3K1 was associated with luminal A status, low-grade histology and low proliferation rates, whereas mutant TP53 was associated with the opposite pattern. Moreover, mutant GATA3 correlated with suppression of proliferation upon aromatase inhibitor treatment. Pathway analysis demonstrated that mutations in MAP2K4, a MAP3K1 substrate, produced similar perturbations as MAP3K1 loss. Distinct phenotypes in oestrogen-receptor-positive breast cancer are associated with specific patterns of somatic mutations that map into cellular pathways linked to tumour biology, but most recurrent mutations are relatively infrequent. Prospective clinical trials based on these findings will require comprehensive genome sequencing.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3383766/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3383766/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ellis, Matthew J -- Ding, Li -- Shen, Dong -- Luo, Jingqin -- Suman, Vera J -- Wallis, John W -- Van Tine, Brian A -- Hoog, Jeremy -- Goiffon, Reece J -- Goldstein, Theodore C -- Ng, Sam -- Lin, Li -- Crowder, Robert -- Snider, Jacqueline -- Ballman, Karla -- Weber, Jason -- Chen, Ken -- Koboldt, Daniel C -- Kandoth, Cyriac -- Schierding, William S -- McMichael, Joshua F -- Miller, Christopher A -- Lu, Charles -- Harris, Christopher C -- McLellan, Michael D -- Wendl, Michael C -- DeSchryver, Katherine -- Allred, D Craig -- Esserman, Laura -- Unzeitig, Gary -- Margenthaler, Julie -- Babiera, G V -- Marcom, P Kelly -- Guenther, J M -- Leitch, Marilyn -- Hunt, Kelly -- Olson, John -- Tao, Yu -- Maher, Christopher A -- Fulton, Lucinda L -- Fulton, Robert S -- Harrison, Michelle -- Oberkfell, Ben -- Du, Feiyu -- Demeter, Ryan -- Vickery, Tammi L -- Elhammali, Adnan -- Piwnica-Worms, Helen -- McDonald, Sandra -- Watson, Mark -- Dooling, David J -- Ota, David -- Chang, Li-Wei -- Bose, Ron -- Ley, Timothy J -- Piwnica-Worms, David -- Stuart, Joshua M -- Wilson, Richard K -- Mardis, Elaine R -- 3P50 CA68438/CA/NCI NIH HHS/ -- P30 CA091842/CA/NCI NIH HHS/ -- P30 CA091842-01/CA/NCI NIH HHS/ -- P50 CA068438/CA/NCI NIH HHS/ -- P50 CA068438-05/CA/NCI NIH HHS/ -- P50 CA094056/CA/NCI NIH HHS/ -- P50 CA094056-10/CA/NCI NIH HHS/ -- P50 CA94056/CA/NCI NIH HHS/ -- R01 CA095614/CA/NCI NIH HHS/ -- R01 CA095614-01A1/CA/NCI NIH HHS/ -- U01 CA114722/CA/NCI NIH HHS/ -- U01 CA114722-01/CA/NCI NIH HHS/ -- U10 CA076001/CA/NCI NIH HHS/ -- U10 CA076001-13/CA/NCI NIH HHS/ -- U54 HG003079/HG/NHGRI NIH HHS/ -- U54 HG003079-04/HG/NHGRI NIH HHS/ -- U54HG003079/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Jun 10;486(7403):353-60. doi: 10.1038/nature11143.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Internal Medicine, Division of Oncology, Washington University, St Louis, Missouri 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22722193" target="_blank"〉PubMed〈/a〉
    Keywords: Androstadienes/pharmacology/therapeutic use ; Antineoplastic Agents/pharmacology/therapeutic use ; Aromatase/*metabolism ; Aromatase Inhibitors/*therapeutic use ; Breast Neoplasms/*drug therapy/*genetics/metabolism/pathology ; DNA Repair ; Exome/genetics ; Exons/genetics ; Female ; Genetic Variation/genetics ; Genome, Human/*genetics ; Humans ; MAP Kinase Kinase 4/genetics ; MAP Kinase Kinase Kinase 1/genetics ; Mutation/genetics ; Nitriles/pharmacology/therapeutic use ; Receptors, Estrogen/metabolism ; Treatment Outcome ; Triazoles/pharmacology/therapeutic use
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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